This invention relates to new and useful carboxylic acid hypoglycemic agents. More particularly, it is concerned with a series of substituted phenylacetic acids and their derivatives, including the base salts of said acids with pharmacologically acceptable cations, which are useful in therapy as oral hypoglycemic agents for the treatment of diabetes. The invention also includes various novel oral pharmaceutical compositions as well as a method of therapy.
In the past, various attempts have been made by numerous investigators in the specialized field of synthetic organic medicinal chemistry to obtain new and better oral hypoglycemic agents. For the most part, these efforts have principally involved the synthesis and testing of various heretofore new and unavailable organic compounds, particularly in the area of the sulfonylureas, in an endeavor to determine their ability to lower blood sugar (i.e., glucose) levels when given by the oral route of administration. However, in the search for new and still more effective antidiabetic agents, far less is known about the effect of non-sulfonylureas and this is particularly so in the case of various carboxylic acid compounds. For instance, G. A. Stewart in Dtsch.-Eng. Med. Rundsch. (Anglo-German Medical Review), Vol. 1, p. 334 (1962) reports that phenylacetic acid is hypoglycemic in normal guinea pigs when given by the oral route of administration at 500 and 750 mg./kg., respectively, while S. Ch. Lahiri et al. in the Journal of the Indian Chemical Society, Vol. 53, p. 1041 (1976) have additionally found that 6-methoxyindan-1-carboxylic acid and 6-methoxyindan-1-acetic acid are both hypoglycemic in normal and alloxan-diabetic rabbits when given by the oral route of administration at dose levels in the neighborhood of 200 mg./kg., respectively. However, none of these prior art compounds possess any outstanding clinical (or even pharmacological) advantages over that of either chlorpropamide or tolbutamide when used in this connection.